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https://hdl.handle.net/123456789/1486| Τύπος: | Άρθρο σε επιστημονικό περιοδικό |
| Τίτλος: | Tissue engineering using vascular organoids from human pluripotent stem cell derived mural cell phenotypes |
| Συγγραφέας: | [EL] Μάρκου, Μαρία[EN] Markou, Maria [EL] Κουρούπης, Δημήτριος[EN] Kouroupis, Dimitrios [EL] Μπαντούνας, Φώτης[EN] Badounas, Fotis [EL] Κατσούρας, Αθανάσιος[EN] Katsouras, Athanasios [EL] Κύρκου, Αθηνά[EN] Kyrkou, Athena [EL] Φώτσης, Θεόδωρος[EN] Fotsis, Theodore [EN] Murphy, Carol [EL] Μπαγκλή, Ελένη[EN] Bagli, Eleni |
| Ημερομηνία: | 17/04/2020 |
| Περίληψη: | Diffusion is a limiting factor in regenerating large tissues (100–200 µm) due to reduced nutrient supply and waste removal leading to low viability of the regenerating cells as neovascularization of the implant by the host is a slow process. Thus, generating prevascularized tissue engineered constructs, in which endothelial (ECs) and mural (MCs) cells, such as smooth muscle cells (SMCs), and pericytes (PCs), are preassembled into functional in vitro vessels capable of rapidly connecting to the host vasculature could overcome this obstacle. Toward this purpose, using feeder-free and low serum conditions, we developed a simple, efficient and rapid in vitro approach to induce the differentiation of human pluripotent stem cellshPSCs (human embryonic stem cells and human induced pluripotent stem cells) to defined SMC populations (contractile and synthetic hPSC-SMCs) by extensively characterizing the cellular phenotype (expression of CD44, CD73, CD105, NG2, PDGFRβ, and contractile proteins) and function of hPSC-SMCs. The latter were phenotypically and functionally stable for at least 8 passages, and could stabilize vessel formation and inhibit vessel network regression, when co-cultured with ECs in vitro. Subsequently, using a methylcellulose-based hydrogel system, we generated spheroids consisting of EC/hPSC-SMC (vascular organoids), which were extensively phenotypically characterized. Moreover, the vascular organoids served as focal starting points for the sprouting of capillary-like structures in vitro, whereas their delivery in vivo led to rapid generation of a complex functional vascular network. Finally, we investigated the vascularization potential of these vascular organoids, when embedded in hydrogels composed of defined extracellular components (collagen/fibrinogen/fibronectin) that can be used as scaffolds in tissue engineering applications. In summary, we developed a robust method for the generation of defined SMC phenotypes from hPSCs. Fabrication of vascularized tissue constructs using hPSC-SMC/EC vascular organoids embedded in chemically defined matrices is a significant step forward in tissue engineering and regenerative medicine. |
| Γλώσσα: | Αγγλικά |
| Σελίδες: | 20 |
| DOI: | 10.3389/fbioe.2020.00278 |
| EISSN: | 2296-4185 |
| Θεματική κατηγορία: | [EL] Βιο- υλικά[EN] Biomaterials |
| Λέξεις-κλειδιά: | cancer; biomaterials; polymer blends; mural cells; tissue engineering; induced pluripotent stem cells; smooth muscle cells; vascularization; vascular organoids; spheroids; regenerative medicine |
| Κάτοχος πνευματικών δικαιωμάτων: | © The Author(s) 2020 |
| Όροι και προϋποθέσεις δικαιωμάτων: | This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Ηλεκτρονική διεύθυνση του τεκμηρίου στον εκδότη: | https://www.frontiersin.org/articles/10.3389/fbioe.2020.00278/full |
| Ηλεκτρονική διεύθυνση περιοδικού: | https://www.frontiersin.org/journals/bioengineering-and-biotechnology |
| Τίτλος πηγής δημοσίευσης: | Frontiers in Bioengineering and Biotechnology |
| Τόμος: | 8 |
| Σελίδες τεκμηρίου (στην πηγή): | Article no 278 |
| Σημειώσεις: | This research supported by (a) the European Social Fund (ESF) and the Greek State [LS7 (2012)]. The research project is implemented within the framework of the Action «Supporting Postdoctoral Researchers» of the Operational Program “Education and Lifelong Learning” (Action’s Beneficiary: General Secretariat for Research and Technology), (b) Greece and the European Union (European Social Fund-ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning 2014–2020» in the context of the project “Generation of distinct phenotypes of mural cells from differentiation of human pluripotent stem cells: application in the generation of vascularized tissueengineered constructs” (5047550). MM was supported by a Ph.D. fellowship from the State Scholarships Foundation (IKY). |
| Εμφανίζεται στις συλλογές: | Ερευνητικές ομάδες |
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